Augmentation of Primary Influenza A Virus-Specific CD8+ T Cell Responses in Aged Mice through Blockade of an Immunoinhibitory Pathway
Augmentation of Primary Influenza A Virus-Specific CD8+ T Cell Responses in Aged Mice through Blockade of an Immunoinhibitory Pathway
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DOI：
10.4049/jimmunol.0903808
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发表时间：
2010-05-15
影响因子：
4.4
通讯作者：
Ertl, Hildegund C. J.
中科院分区：
文献类型：
--
作者：
DiMenna, Lauren;Latimer, Brian;Ertl, Hildegund C. J.
免疫反应随着年龄的增长而减少，导致老年人对感染性物质的易感性增加，无法对疫苗产生保护性免疫反应。免疫衰老影响免疫系统的多个方面，包括CD8(+)T细胞，它们控制病毒感染，并被认为可以防止癌症的发展。在这项研究中，我们测试了是否可以通过一种同时表达抗原和阻断免疫抑制途径的分子的疫苗来增强老龄小鼠的CD8(+)T细胞反应。具体地说，我们测试了一种基于复制缺陷的黑猩猩来源的腺病毒载体的疫苗，该载体将甲型流感病毒核蛋白(NP)表达为与单纯疱疹病毒1型糖蛋白D的融合蛋白，后者通过与疱疹病毒进入介体结合，阻断免疫抑制的疱疹病毒进入介体B和T淋巴细胞衰减器/CD160途径。我们的结果表明，与仅表达NP的疫苗相比，表达NP和糖蛋白D融合蛋白的疫苗在幼年和老年小鼠中诱导了显著更高的NP特异性CD8(+)T细胞应答。《免疫学杂志》，2010,184：5475-5484。
Immune responses diminish with age resulting in an increased susceptibility of the elderly to infectious agents and an inability to mount protective immune responses to vaccines. Immunosenescence affects multiple aspects of the immune system, including CD8(+) T cells, which control viral infections and are assumed to prevent the development of cancers. In this study, we tested if CD8(+) T cell responses in aged mice could be enhanced through a vaccine that concomitantly expresses Ag and a molecule that blocks an immunoinhibitory pathway. Specifically, we tested a vaccine based on a replication-defective chimpanzee-derived adenovirus vector expressing the nucleoprotein (NP) of influenza A virus as a fusion protein with the HSV type 1 glycoprotein D, which through binding to the herpes virus entry mediator, blocks the immunoinhibitory herpes virus entry mediator B and T lymphocyte attenuator/CD160 pathways. Our results show that the vaccine expressing a fusion protein of NP and glycoprotein D induces significantly higher NP-specific CD8(+) T cell responses in young and aged mice compared with the vaccine expressing NP only. The Journal of Immunology, 2010, 184: 5475-5484.